星希亞的抗癌日誌

第17屆肺癌世界大會(WCLC, World Conference on Lung Cancer)於2016年底在維也納舉辦，Poster Session中有一篇文章提供ALK癌友參考。若有自費吃Ceritinib(Zykadia, LDK378)的癌友，建議一定要看喔！

ref: https://library.iaslc.org/

Phase 1 Study of Ceritinib 450 mg or 600 mg Taken with a Low-Fat Meal versus 750 mg in Fasted State in ALK+ Metastatic NSCLC

R. Dziadziuszko, D. Kim, A. Bearz, S.A. Laurie, M. McKeage, K. Park, S. Kim, V.Q. Passos, K. Osborne, Y.Y. Lau, J. Gu, B.C. Cho

Background: 
The anaplastic lymphoma kinase (ALK) inhibitor ceritinib is approved at 750 mg fasted for the treatment of patients with ALK-rearranged (ALK+) metastatic non-small cell lung cancer (NSCLC) pretreated with crizotinib. The pharmacokinetic (PK) part of this study (Part 1) compares PK exposure of ceritinib following food consumption versus a fasted state in advanced ALK+ NSCLC patients.

Methods: 
Part 1 of this prospective, open-label, multicenter, randomized, 3-arm, phase 1 study (ASCEND-8; NCT02299505) is investigating PK and safety of ceritinib in advanced ALK+ NSCLC patients, treatment-naïve or pretreated with multiple lines of chemotherapy and/or crizotinib. Here, we compare steady-state PK of ceritinib 450 or 600 mg taken with a low‑fat meal versus ceritinib 750 mg fasted (primary endpoint) and report preliminary safety outcomes from Part 1. Part 2 continues to randomize treatment-naïve patients and will assess safety and efficacy.

Results: 
As of June 16, 2016 (data cut-off), 137 patients were randomized in a 1:1:1 ratio to each treatment arm; 135 patients received one dose (safety set) and 97 patients had evaluable steady-state PK data. Disease characteristics were comparable between arms. Median follow-up duration was 4.14 months (range, 0.1–13.9). Relative to 750 mg fasted, the 450 mg fed arm demonstrated comparable steady-state PK, while the 600 mg fed arm showed ~25% higher steady-state PK (Table). Preliminary safety data suggests overall frequency of AEs and types of AEs were comparable between arms. However, incidences of gastrointestinal (GI)-related AEs (diarrhea, nausea or vomiting) were lowest, with no grade 3/4 GI AEs reported, in the 450 mg fed arm.

Figure 1

 

Conclusion: 

Steady-state PK was comparable in advanced ALK+ NSCLC patients taking ceritinib 450 mg with a low-fat meal versus 750 mg fasted. This study continues to enroll treatment-naïve patients into Part 2 to assess efficacy across the three treatment arms and assess longer safety follow-up.

---

Cincia重點說明一下：

<研究背景>

本研究主要想了解Ceritinib不同服藥方式(空腹狀態 vs. 用餐後)下，藥物動力學的差異。

<研究方法>

將ALK+病人分成三組：450mg Ceritinib (隨著低脂食物)、600mg Ceritinib(隨著低脂食物)、750mg Ceritinib(空腹狀態)。

註：諾華藥廠藥單建議為750mg(空腹服用)。

<研究結果>

137名病患中，97名獲得穩定可評估之數據。

  

以藥物動力學兩個參數來看，不管是AUC_0-24h(24小時血中濃度曲線下面積)或Cmax (血中濃度最大值)，450mg飲食組和750mg空腹組的數據均相當，而600mg飲食組則為750mg空腹組的1.25倍。

用藥安全的部分，副作用的頻度和類型各組相當；然而450mg飲食組在胃腸道相關的副作用（腹瀉、噁心或嘔吐）最低，沒有3級/4級副作用*的案例。

*藥物副作用的定義是由美國癌症研究院制訂的 Common Terminology Criteria for Adverse Events (CTCAE, 又稱常見毒性標準), 用於描述病人接受癌症治療後，所發生器官毒性的嚴重度分級。分為輕微 (1級)、中級 (2級)、嚴重(3級), 或致命( 4級)、死亡 ( 5級)。